Virome Analysis of Transfusion Recipients Reveals a Novel Human Virus That Shares Genomic Features with Hepaciviruses and Pegiviruses.
Virome Analysis of Transfusion Recipients Reveals a Novel Human Virus That Shares Genomic Features with Hepaciviruses and Pegiviruses.
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DOI：
10.1128/mbio.01466-15
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发表时间：
2015-09-22
期刊：
影响因子：
6.4
通讯作者：
Lipkin WI
中科院分区：
文献类型：
--
作者：
Kapoor A;Kumar A;Simmonds P;Bhuva N;Singh Chauhan L;Lee B;Sall AA;Jin Z;Morse SS;Shaz B;Burbelo PD;Lipkin WI
为了解新型感染病原体通过输血传播的情况，我们研究了输血受血者输血前后病毒组分的变化。利用这种方法，我们检测到一种新的人类病毒，人类巨细胞病毒1型(HHpgV-1)，它与丙型肝炎病毒(HCV)和人类巨细胞病毒(HPgV；以前称为GB病毒C或G型肝炎病毒)有共同的特征。丙型肝炎病毒和人乳头瘤病毒同属黄病毒科肝病毒属和巨细胞病毒属。在两名输血接受者和两名接受血浆来源凝血因子浓缩的血友病患者的血清样本中发现了HHpgV-1。前者仅在输血后样本中检测到该病毒，表明该病毒是通过血液传播的。这两名血友病患者都在至少201天和1,981天内持续存在病毒症。HHpgV-1的5‘非翻译区(UTR)含有IV型内部核糖体进入位点(IRES)，与丙型肝炎病毒和其他肝炎病毒的结构相似，但在序列上有很大的差异。然而，非结构基因(NS3和NS5B)的系统发育分析表明，HHpgV-1在PEGV分支内形成了一个分支，不同于HPgV和感染其他哺乳动物的同源物。与一些感染啮齿动物和蝙蝠的巨型病毒变体一样，HHpgV-1基因组编码一种位于E1上游的短的、高度碱性的蛋白质，在组装过程中可能具有包装RNA的核心样功能。这种新的人类病毒HHpgV-1的发现扩大了我们对这些病毒基因组构型范围的了解，并可能导致对定义肝炎病毒属和PEGI病毒属的原始标准的重新评估。仅在美国，每年就有超过3000万份血液成分被输注。监测血液供应中的感染性病原体是确保这一药品和公共卫生关键资源安全的关键。在这里，我们报告了从人血清样本中鉴定出一种新的高度多样化的丙型肝炎病毒/GB病毒(GBV)样病毒。在输血受血者的血清样本中发现了这种新的人类疱疹病毒1型(HHpgV-1)，这表明它可能通过输血产品传播。我们还在两名血友病患者中发现了持续性的长期HHpgV-1病毒血症。HHpgV-1是独一无二的，因为它与高致病性丙型肝炎病毒和明显非致病性HPgV(GBV-C)具有遗传相似性。我们的结果增加了人类病毒的名单，并为开发研究病毒传播和疾病关联的试剂以及阻断病毒传播和新的人类感染提供了数据。
To investigate the transmission of novel infectious agents by blood transfusion, we studied changes in the virome composition of blood transfusion recipients pre- and posttransfusion. Using this approach, we detected and genetically characterized a novel human virus, human hepegivirus 1 (HHpgV-1), that shares features with hepatitis C virus (HCV) and human pegivirus (HPgV; formerly called GB virus C or hepatitis G virus). HCV and HPgV belong to the genera Hepacivirus and Pegivirus of the family Flaviviridae. HHpgV-1 was found in serum samples from two blood transfusion recipients and two hemophilia patients who had received plasma-derived clotting factor concentrates. In the former, the virus was detected only in the posttransfusion samples, indicating blood-borne transmission. Both hemophiliacs were persistently viremic over periods of at least 201 and 1,981 days. The 5′ untranslated region (UTR) of HHpgV-1 contained a type IV internal ribosome entry site (IRES), structurally similar to although highly divergent in sequence from that of HCV and other hepaciviruses. However, phylogenetic analysis of nonstructural genes (NS3 and NS5B) showed that HHpgV-1 forms a branch within the pegivirus clade distinct from HPgV and homologs infecting other mammalian species. In common with some pegivirus variants infecting rodents and bats, the HHpgV-1 genome encodes a short, highly basic protein upstream of E1, potentially possessing a core-like function in packaging RNA during assembly. Identification of this new human virus, HHpgV-1, expands our knowledge of the range of genome configurations of these viruses and may lead to a reevaluation of the original criteria by which the genera Hepacivirus and Pegivirus are defined. More than 30 million blood components are transfused annually in the United States alone. Surveillance for infectious agents in the blood supply is key to ensuring the safety of this critical resource for medicine and public health. Here, we report the identification of a new and highly diverse HCV/GB virus (GBV)-like virus from human serum samples. This new virus, human hepegivirus 1 (HHpgV-1), was found in serum samples from blood transfusion recipients, indicating its potential for transmission via transfusion products. We also found persistent long-term HHpgV-1 viremia in two hemophilia patients. HHpgV-1 is unique because it shares genetic similarity with both highly pathogenic HCV and the apparently nonpathogenic HPgV (GBV-C). Our results add to the list of human viruses and provide data to develop reagents to study virus transmission and disease association and for interrupting virus transmission and new human infections.